Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.
Lancet Haematol
; 5(6): e241-e251, 2018 Jun.
Article
en En
| MEDLINE
| ID: mdl-29780001
ABSTRACT
BACKGROUND:
There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens.METHODS:
This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30â×âdepth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15â×âdepth) with serological comparisons.FINDINGS:
We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage).INTERPRETATION:
By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.FUNDING:
National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Sistema del Grupo Sanguíneo Rh-Hr
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Sistema del Grupo Sanguíneo ABO
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Tipificación y Pruebas Cruzadas Sanguíneas
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Antígenos de Plaqueta Humana
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Secuenciación Completa del Genoma
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Idioma:
En
Revista:
Lancet Haematol
Año:
2018
Tipo del documento:
Article